Exploration of SARS-CoV-2 Mpro Noncovalent Natural Inhibitors Using Structure-Based Approaches.

With the emergence of antibody-evasive omicron subvariants (BA.2.12.

2D-quantitative structure-activity relationships model using PLS method for anti-malarial activities of anti-haemozoin compounds.

Background: Emergence of cross-resistance to current anti-malarial drugs has led to an urgent need for identification of potential compounds with novel modes of action and anti-malarial activity against the resistant strains. One of the most promising therapeutic targets of anti-malarial agents related to food vacuole of malaria parasite is haemozoin, a product formed by the parasite through haemoglobin degradation.

Methods: With this in mind, this study developed two-dimensional-quantitative structure-activity relationships (QSAR) models of a series of 21 haemozoin inhibitors to explore the useful physicochemical parameters of the active compounds for estimation of anti-malarial activities.

Exploring Aurone Derivatives as Potential Human Pancreatic Lipase Inhibitors through Molecular Docking and Molecular Dynamics Simulations.

Inhibition of human pancreatic lipase, a crucial enzyme in dietary fat digestion and absorption, is a potent therapeutic approach for obesity treatment. In this study, human pancreatic lipase inhibitory activity of aurone derivatives was explored by molecular modeling approaches. The target protein was human pancreatic lipase (PDB ID: 1LPB).

Correlation between anti-malarial and anti-haemozoin activities of anti-malarial compounds.

Background: Despite noticeable improvement in anti-malarial treatment, rapid growth of resistant malaria strains points out the need for continuous development of novel anti-malarials to fight the disastrous infection. Haemozoin is considered as a novel inhibitory pathway for new anti-malarial drugs, therefore, this study aimed to systematically review all articles investigating the correlation between anti-malarial and anti-haemozoin activities of anti-malarial compounds.

Methods: A literature search was conducted on 22 October 2017 in eight databases for relevant in vitro articles reporting the correlation between anti-malarial and anti-haemozoin of anti-malarial compounds, based on the constructed search terms and inclusion criteria.

Molecular Docking Studies of Glycyrrhetinic Acid Derivatives as Anti- Colorectal Cancer Agents.

Background: In this study, the anti-colorectal cancer (CRC) activities of 40 glycyrrhetinic acid derivatives were proposed and evaluated by the molecular docking method, which allowed the flexibility of both ligand-receptor, with twelve CRC-related targets.

Methods: The proposed derivatives, which clearly distinguish isomers at position 18 as well as the different tautomers, were divided into five groups, including (1) glycyrrhetinic acid and its oxidation derivatives, (2) glycoside derivatives, (3) 3β-amine derivatives, (4) five-membered heterocyclic ring-combined derivatives, and (5) six-membered heterocyclic ring-combined derivatives.

Results: Finally, four out of twelve proposed targets related to CRC with good binding affinities to the proposed glycyrrhetinic acid derivatives were selected, including Epidermal Growth Factor Receptor (EGFR), Focal Adhesion Kinase (FAK), Lactate Dehydrogenase A (LDHA), and Thymidylate Synthase (TS).

Molecular Docking Studies to Explore Potential Binding Pockets and Inhibitors for Chikungunya Virus Envelope Glycoproteins.

The chikungunya virus (CHIKV) envelope glycoproteins are considered important potential targets for anti-CHIKV drug discovery due to their crucial roles in virus attachment and virus entry. In this study, using two available crystal structures of the immature and mature forms of envelope glycoproteins, virtual screenings based on blind dockings and focused dockings were carried out to identify potential binding pockets and hit compounds for the virus. The chemical library database of compounds, NCI Diversity Set II, was used in these docking studies.

Identification of chikungunya virus nsP2 protease inhibitors using structure-base approaches.

The nsP2 protease of chikungunya virus (CHIKV) is one of the essential components of viral replication and it plays a crucial role in the cleavage of polyprotein precursors for the viral replication process. Therefore, it is gaining attention as a potential drug design target against CHIKV. Based on the recently determined crystal structure of the nsP2 protease of CHIKV, this study identified potential inhibitors of the virus using structure-based approaches with a combination of molecular docking, virtual screening and molecular dynamics (MD) simulations.

Discovery of in silico hits targeting the nsP3 macro domain of chikungunya virus.

The recent emergence and re-emergence of alphaviruses, in particular the chikungunya virus (CHIKV), in numerous countries has invoked a worldwide threat to human health, while simultaneously generating an economic burden on affected countries. There are currently no vaccines or effective drugs available for the treatment of the CHIKV, and with few lead compounds reported, the vital medicinal chemistry is significantly more challenging. This study reports on the discovery of potential inhibitors for the nsP3 macro domain of CHIKV using molecular docking, virtual screening, and molecular dynamics simulations, as well as work done to evaluate and confirm the active site of nsP3.